Ingestible formulations for transient, noninvasive reduction of gastric volume

ABSTRACT

Provided are ingestible polymeric formulations and oral dosage forms for the reduction of gastric volume in the treatment of overweight and obese patients. The formulation includes an acid-sensitive, gelatin coating over a dehydrated hydrophilic polymer. When ingested, the acid-sensitive coating is quickly dissolved by gastric secretions and the hydrophilic polymer is exposed to the aqueous environment of the gastric milieu. The polymer absorbs water and expands to the point that will not allow the polymer to pass beyond the pyloric valve, and the expanded polymer is therefore trapped in the stomach.

This application is a divisional of U.S. application Ser. 12/148,702filed Jan. 25, 2008, which is a continuation of U.S. application Ser.No. 10/741,177, filed Dec. 19, 2003, which claims the benefit ofpriority under 35 U.S.C. §119(e) of U.S. Ser. No. 60/468,131 filed May6, 2003, and U.S. Ser. No. 60/434,367 filed Dec. 19, 2002, the entirecontents of which are incorporated herein by reference.

FIELD OF THE INVENTION

The invention relates generally to polymeric formulations, especiallypolymers useful for weight loss methods and devices.

BACKGROUND OF THE INVENTION

Obesity is a condition of epidemic proportions in the United States.Recent government studies have indicated that up to 40% of Americans areobese, and of those, almost 20% are morbidly obese. In and of itself,however, obesity is not the problem. The difficulty with obesity ariseswith the multiple conditions, including cardiovascular disease,diabetes, and obstructive sleep apnea, that occur with this ubiquitousproblem. There have been many attempts to treat obesity, most of whicheither have serious side effects or are ineffective.

For example, various diets, supplements, and pharmaceuticals have beendeveloped in an attempt to treat obesity. Typically, these types oftreatment have not provided any significant benefit. Indeed, some weightloss pharmaceuticals have been associated with many seriouslife-threatening conditions. To date, there are no commerciallyavailable supplements or drugs on the market that have been found tohave significant success in weight reduction.

Recognizing this, the medical industry has turned to more extrememeasures, the best example of which is the Roux-En-Y gastric bypass.More effective, but also potentially lethal, this major surgery with1-2% mortality, 6 month recovery period and a price tag of tens ofthousands of dollars, is still increasing in its popularity due to theinefficacy of other treatments. Gastric reduction, or simply removing alarge segment of the stomach, is similar to gastric bypass in itspotentially lethal combinations.

Progress was made, however, with the introduction of intragastricballoons, as described in U.S. Pat. Nos. 4,739,758; 5,234,454;4,485,805; and 4,899,747. These balloons, designed to be placedsurgically or endoscopically, are constructed of silicone and inflatedonce positioned in the stomach, thereby reducing effective gastricvolume. These balloons were found to be effective in increasing thesensation of fullness in the patient and reducing weight by reducingintake.

Unfortunately, these intragastric balloons still required an invasiveprocedure and also generated ulcers and other complications due tohaving the inflexible silicone surface in contact with the stomach wallin the same orientation for months. Also, these devices require furtherinvasive surgery or endoscopic procedures to reduce or increase theballoon volume in the common event that the balloon was filled too muchor too little.

A further advancement was proposed by Ratjen in German Patent No.NDN-050003290517 in which a compressed cellulose derivative wasutilized. This compressed cellulose derivative was coated with gelatinand was designed to be expanded once ingested into the stomach. Thedifficulty with this derivation is that cellulose is broken down atroughly equivalent rates in the stomach and small bowel. Thus, anypartially digested masses of cellulose that have been passed from thestomach will remain intact in the intestine and cause a possible smallbowel obstruction. This risk outweighs the possible benefit, in manycases making the therapy undesirable.

A similar difficulty is likely to be associated with the therapydescribed in U.S. Pat. Nos. 5,750,585 and 6,271,278. The polymersdescribed therein do not exhibit differential degradation rates in thestomach and the intestine, thereby placing patients at risk for a smallbowel obstruction. Therefore, there is a need in the industry to developmore methods and devices, especially noninvasive methods and devicesuseful for weight loss and/or weight management.

SUMMARY

The present invention is based, in part, on the discovery that certainpolymers can be modified so that they have a higher degradation rate inan intestine-like environment than in a gastric-like environment, whoseenzymatic and pH make up is different from each other. Accordingly thepresent invention provides polymeric formulations capable of beingretained in a stomach for a certain period of time and being rapidlydegraded upon entering into an intestine. The polymeric formulationsprovided by the present invention can be used for various applicationsincluding delivery of therapeutics, e.g., in a stomach over a period oftime, and reduction of gastric volume in the treatment of overweight andobese patients.

In one embodiment of the invention, there are provided oral dosage formsuseful for gastric volume reduction. Such oral dosage forms, include,for example, a polymer that (i) swells upon absorbing water from gastricfluid to increase its size thereby promoting its gastric retention, (ii)maintains its physical integrity in a stomach for about 4 hours to 30hours, and (iii) is degradable by an intestinal enzyme or exposure to anintestinal pH, e.g., 8.0, wherein the dosage form is in the form of atablet or capsule that maintains the polymer in a packed mass prior toits ingestion and then rapidly disintegrates in the gastric fluid topermit the polymer to disperse in the stomach and wherein the dosageform does not contain a drug.

In another embodiment, there are provided polymeric formulationsincluding a hydrophilic polymer that (i) swells upon absorbing waterfrom gastric fluid to increase its size thereby promoting its gastricretention, (ii) maintains its physical integrity in a stomach for atleast 2 hours, e.g., from 2 to 30 hours, and (iii) degrades faster in anintestine than a stomach, wherein the polymer is cross linked through alinker which provides the polymer with a sensitivity towards anintestinal enzyme.

In still further embodiments, there are provided methods for reducinggastric volume in a subject. Such methods can be performed, for example,by administering to a subject in need thereof an oral dosage formdescribed herein. In an alternative embodiment, such methods can beperformed by administering to a subject in need thereof a polymericformulation described herein.

In yet another embodiment, there are provided methods for delivering adrug. Such methods can be performed, for example, by administering to asubject in need of the drug a polymeric formulation described herein,wherein the formulation further contains the drug dispersed in thepolymer.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a cross-sectional view of an oral dosage form in tabletform.

FIGS. 2A-2B shows cross-sectional views of the stomach illustrating theingestion of the polymeric formulation of the invention and itssubsequent expansion in the stomach.

FIGS. 3A-3B shows cross-sectional views of the stomach illustrating theingestion of multiple tablets of the polymeric formulation of theinvention and subsequent expansion in the stomach.

FIGS. 4A-4B shows cross-sectional views of the stomach illustrating thepresence of multiple tablets polymeric formulations of the invention invarious stages of degradation with one tablet sufficiently degraded topass the pyloric valve and be rapidly degraded in the small intestinemilieu.

FIGS. 5A-5B shows cross-sectional views of the stomach illustrating thepresence of a hydrated polymer and the ingestion of a depolymerizer.

DETAILED DESCRIPTION OF THE INVENTIONS

The present invention provides polymeric formulations capable of beingretained in a gastric like environment for a certain period of time andbeing rapidly degraded upon entering into an intestine like environment.Specifically the present invention provides oral dosage forms andpolymeric formulations useful for reduction of gastric volume in thestomach or delivering therapeutics to a subject, e.g., human.

The polymers utilized in the oral dosage forms and formulations of theinvention are capable of being degraded differentially in an intestinelike environment as compared to a gastric like environment. For example,the polymers of the present invention degrades faster in an environmentwith an enzymatic and/or pH make up characteristic of the intestine thanthat of the stomach. Usually such differential degradation is based onpH sensitivity of an entity or an entity's sensitivity to one or moreintestinal specific substances, such as, bile, lipases, and otherintestinal enzymes or entities and the like.

Sensitivity to intestinal enzymes or pH can be obtained by any suitablemeans available to one skilled in the art, e.g., chemical modification.For example, sensitivity to intestinal enzymes, e.g., lipases can beachieved through chemical modification of either natural entities, e.g.,alginate, cellulose, and the like or modification of artificiallysynthesized entities, e.g., an acrylate. By acquiring one or morelipase-sensitive, fatty acid-like polymerizable groups and/orcross-linking groups, an entity can have optimal differentialdegradation characteristics in which degradation occurs much morerapidly in the intestine as compared to the gastric environment.Alternatively, differential degradation can be accomplished viaincorporation of components that are selectively degraded in theintestine, e.g., fats, and need not be limited to proteins and polymers.

The oral dosage form or polymeric formulation of the present inventionusually can include an acid-sensitive, gelatin coating over a dehydratedhydrophilic polymer. When ingested, the acid-sensitive coating isquickly dissolved by gastric secretions and the hydrophilic polymer isexposed to the aqueous environment of the gastric milieu. The polymerabsorbs water and expands to the point that will not allow the polymerto pass beyond the pyloric valve, and the expanded polymer is thereforetrapped in the stomach. The expanded polymer remains in the stomachuntil acids and proteases or other enzymes in the stomach reduce itsvolume such that it is able to pass the pyloric valve into theintestine.

Although the polymeric formulation of the present invention is designedto be somewhat resistant to degradation by gastric secretions, itremains highly susceptible to the environment of the intestine, e.g.,intestinal enzymes or pH. Thus, while the polymeric formulation of thepresent invention can remain in the stomach for many hours or even days,once it has passed into the intestine, it is rapidly degraded, therebyreducing the risk of small bowel obstruction. Since the polymer of thepresent invention degrades much more rapidly in an intestinalenvironment than in the stomach, the potential risk of small bowelobstruction is significantly reduced or virtually eliminated.

In addition, the formulations and dosage forms of the invention aredesigned to expand to a diameter that is sufficient to prevent passagebeyond the pyloric valve, but will not cause small bowel obstruction orrupture, e.g., a diameter no greater than about 6 cm or so. Due to thissize restriction, use of the present invention entails ingestion ofmultiple tablets until the subject begins to feel a sensation offullness. The present invention avoids the complications of excessivegastric distension that is common after intragastric balloon placement.Once the oral dosage forms and polymeric formulations described hereinpass beyond the pyloric valve and are degraded in the intestine, thesubject simply ingests additional tablets.

According to one feature of the present invention, it provides oraldosage forms of polymers useful for gastric volume reduction. The oraldosage form of the present invention includes a polymer that (i) swellsupon absorbing water from gastric fluid to increase its size therebypromoting its gastric retention, (ii) maintains its physical integrityin the stomach for a period of time and (iii) is degradable by anintestinal enzyme or exposure to an intestinal pH. The dosage form ofthe present invention can be in the form of a tablet or capsule, e.g.,maintains the polymer in a packed mass prior to its ingestion and thenrapidly disintegrates in the gastric fluid to permit the polymer todisperse in the stomach. In one embodiment, the dosage form of thepresent invention does not contain a drug. In another embodiment, theoral dosage form of the present invention maintains its physicalintegrity for at least 2 hours, 4 hours, or 6 hours. In yet anotherembodiment, the oral dosage form of the present invention maintains itsphysical integrity from about 4 hours to 30 hours, 6 hours to 24 hours,or 8 hours to 16 hours.

As used herein, the phrase “gastric volume reduction” means 1) anytemporary reduction of available gastric volume, e.g., any temporaryreduction of gastric volume available to an ingested subject, 2) anytemporary reduction of gastric capability with respect to contentintake, or 3) any temporary sensation of gastric fulfillment orfullness.

As used herein, the phrase “physical integrity”, when used withreference to the polymers described herein, means that the polymers donot significantly or appreciably dissolve, erode or otherwise decomposeor degrade, e.g., the polymer chains remain substantially intact, and,if the polymers are cross-linked, that the cross-links remainsubstantially intact, thereby providing a three-dimensional polymericnetwork.

Polymers contemplated for use in the practice of the invention aretypically water-soluble polymers or co-polymers, e.g., polymers orcopolymers capable of swelling upon contacting with water. Such polymersinclude, for example, polyvinyl alcohol, poly(ethyloxazoline),poly(2-hydroxy ethylacrylate), poly(2-hydroxy ethylmethacrylate),polyacrylic acid, polysaccharides, proteins, polynucleic acids, and thelike. In one embodiment, the polymers of the present invention ispolyvinylacetate-polyvinylalcohol copolymers, poly(2-hydroxyethylacrylate) and copolymers, poly(ethyloxazoline) and copolymers, orpoly(2-hydroxyethylmethacrylate) and copolymers.

As used herein, the term “polysaccharides” includes polysaccharides,polysaccharoses, sugars, and the like. Exemplary polysaccharides includestarch, sodium starch glycolate, alginic acid, cellulose,carboxymethylcellulose, hydroxyethylcellulose, hydropropylcellulose,hydroxypropylmethylcellulose, ethylcellulose, carageenan, chitosan,chondroitin sulfate, heparin, hyaluronic acid, pectinic acid, chitosan,hyaluronic acid, xanthan gum, starch, maltodextrins, corn syrup,alginates, and the like. Proteins contemplated for use include, but arenot limited to, water soluble proteins, e.g., albumin, gelatin, and thelike.

According to one embodiment of the present invention, the oral dosageform or polymeric formulation of the present invention includes apolymer that is biocompatible and/or pH sensitive, e.g., sensitive tointestinal pH. Such oral dosage form or polymeric formulation typicallyincludes a dehydrated combination of a biocompatible polymer, e.g., analginate and a solubilizer/stabilization agent, e.g., xanthan gum,propylene glycol alginate, and the like (to allow for maintenance of afirm solid polymer within the gastric environment) covered with anacid-sensitive coating (e.g., a gelatin). Alginate itself precipitatesto a certain degree in the acidic environment of the stomach and solikely requires an additional component in order to preventprecipitation. In one embodiment, the additional component is propyleneglycol alginate. In another embodiment, the solubilizer/stabilizationagent is sensitive to intestinal pH. For example, propylene glycolalginate forms a solid in the stomach but becomes viscous at intestinalpH. Typically, about half of the polymer of alginate with propyleneglycol alginate is degraded after 3 to 4 hours at intestinal pH.

According to another embodiment of the present invention, the polymersdescribed herein are cross-linked. Cross-linking can be achieved eitherthrough a covalent cross-linker or non-covalent cross-linker. Typicalthe covalent cross-linker of the present invention includes, forexample, homobifunctional cross-linkers with reactive molecules ofdiglycidyl ethers, substituted and unsubstituted diN-hydroxysuccinimides (NHS), diisocyanates, diacids, diesters, diacid chlorides,dimaleimides, diacrylates, and the like. Heterobifunctionalcross-linkers can also be utilized. Heterobifunctional cross-linkersusually include molecules that contain different functional groups toaccomplish the cross-linking, for example, combining NHS and maleimide,an acid and ester, etc.

Non-covalent cross-linkers, e.g., based on ionic, hydrogen bonding andother intramolecular associations are also contemplated for use in thepractice of the invention. The non-covalent cross-linkers of the presentinvention include chitosan/polyacrylic acid, polyacrylicacid/polyethylene glycol (at low pH), polyacrylic acid copolymers andhydroxyl containing polymers, polymers containing carboxylic acidpendant groups, pluronics (ethylene oxide-propylene oxide-ethylene oxide(EO-PO-EO) triblock copolymers), metal cross-linked polymers, ionomers,and the like. For example, the non-covalent cross-linkers of the presentinvention can be based on hydrophobic associations. Such non-covalentcross-linkers can be any suitable system that demonstrates lowercritical association temperatures including, without any limitation,pluronics (triblock copolymers of ethylene oxide and propylene oxidestructured as EO-PO-EO), which can form gels at elevated temperaturessuch as body temperature and convert to a soluble form at a lowertemperature such as room temperature.

In one embodiment, the cross-linker of the present invention containsone or more hydrolysable groups. In another embodiment, the cross-linkerof the present invention is susceptible to hydrolysis, e.g., either bychemical means or by biological means such as enzyme catalyzedhydrolysis. In yet another embodiment, the cross-linker of the presentinvention is a polymer or copolymer of lactic acid, glycolic acid,trimethylene carbonate, caprolactone, or any other hydrolysable esters.

In still another embodiment, the cross-linker of the present inventionincludes a linker between the cross-linking functionalities that rendersthe ultimate cross-linked polymer a degradation susceptibility towardsan intestinal enzyme, e.g., susceptibility to degradation by anintestinal enzyme. These types of cross-linkers typically include basicsensitive groups or C.sub.12-C.sub.22 aliphatic unsaturated hydrocarbonlinkers, since an intestinal enzyme such as a lipase recognizes fattyacid type structures. In some embodiments, these linkers include diacidsthat form alpha-omega ester linkages between polymer chains, therebycross-linking the polymer chains. In addition, oligoesters havingalternating PEG spacers can be utilized. Indeed, PEG chains or otherhydrophilic spacers can be incorporated into the cross-linkers of thepresent invention to control hydrophilicity and swelling of the polymersprovided by the present invention.

According to another embodiment of the present invention, the polymerused in the present invention can be any polymer that degrades faster inan environment with an intestinal pH, e.g., pH 8. In one embodiment, thepolymer of the present invention can be cross-linked hydrogelformulations that are held together by physical cross-links between acidgroups and ether oxygens. Examples of acid containing polymers includecarboxymethylcellulose, agarose, polyacrylic acid and copolymers, etc.Polymers containing ether oxygens include, for example, any PEGs(branched or linear), any PEG copolymers including, without anylimitation, pluronics, polysaccharides, starches, etc.

In another embodiment, the polymer of the present invention includes anypolymer containing pendant acid groups or chemically hydrolysablegroups. For example, polymers containing one or more pendant acidgroups, e.g., carboxymethylcellulose, agarose, polyacrylic acid andcopolymers etc. and/or chemically hydrolysable groups, e.g., anhydrides,ketals, acetals, and esters can be covalently cross-linked. In general,as the pH increases in an environment the hydrolyzability of the estergroups in these polymers can increase due to their increasedaccessibility caused by the polymeric swelling.

With specific reference now to the figures, FIG. 1 shows across-sectional view of an oral dosage form of the invention in tabletform. Specifically, FIG. 1 shows the ingestible compound 1 including adissolvable coating 2 surrounding the desiccated polymeric formulation3. In FIGS. 2A and 2B, the tablet is shown functioning in the stomach.In FIG. 2A, the ingestible tablet 1 of FIG. 1 is shown passing the loweresophageal sphincter 5 into the stomach. In FIG. 2B, the tablet 1 isshown after its coating 2 has dissolved and the tablet 1 has expanded toits hydrated form 4. The expanded polymer 4 cannot pass either the loweresophageal sphincter 5 or the pyloric sphincter 6 resulting in itsretention in the stomach.

In FIGS. 3A-B, multiple tablets are shown functioning in the stomach. InFIG. 3A, the ingestible tablets 1 of FIG. 1 are shown passing the loweresophageal sphincter 5 into the stomach. In FIG. 3B, the tablets 1 areshown after their coatings 2 have dissolved and the tablets 1 haveexpanded to their hydrated forms 4. The expanded polymers 4 cannot passeither the lower esophageal sphincter 5 or the pyloric sphincter 6resulting in its retention in the stomach. Obese patients can take asmany tablets 1 as are required to produce a sensation of fullness.

In FIG. 4A, multiple polymeric masses 4 are shown in the stomach invarious stages of degradation. One of the masses 10 has degradedsufficiently to pass the pyloric sphincter 6. In FIG. 4B, the polymericmasses 4 are shown in the stomach again with the smallest mass beingrapidly degraded in the small intestine to its polymeric precursors 7after passing the pyloric sphincter 6.

In FIGS. 5A-B, the polymer is shown being de-polymerized after itsplacement in the stomach. In FIG. 5A, the hydrated polymer 4, whichcannot pass either the lower esophageal sphincter 5 or the pyloricsphincter 6, is shown in the stomach as de-polymerizer 8 is introduced.The de-polymerizer 8 is shown in tablet form, but may also be in liquidform. In FIG. 5B the de-polymerizer has acted on the polymer 4 resultingin de-polymerization to the polymeric precursors 7. In the case of thealginates and other pH-sensitive groups, the de-polymerizer 8 is acompound which simply raise the pH. In the case of lipid-modifiedpolymers (e.g., acrylates, alginates, cellulose, and the like), thede-polymerizer 8 is a commercially available pharmaceutical gradelipase.

The oral dosage forms and polymeric formulations described hereintypically achieve 90% of equilibrium swelling in about 6-18 hours, andtypically have completely disappeared from the gut in about 3-10 days.The dosage forms and formulations typically contain an enteric coatingso that expansion occurs only in the stomach, and not in the esophagus.Invention oral dosage forms and polymeric formulations typically exhibitswelling resulting in a size increase of about 200%-1000%.

The present invention allows for the safe, controlled distension of thestomach in a noninvasive and completely reversible manner. The oraldosage forms described herein usually include an enterically coatedpolymeric formulation that is small enough to be swallowed in itspre-gastric state. Once the polymeric formulation reaches the stomach,the coating is dissolved by gastric secretions and the polymer ishydrated resulting in significant swelling, enough so that the resultinghydrated polymer cannot pass the pyloric valve and remains in thestomach.

The oral dosage forms are designed such that the obese patient cansimply continue to ingest additional dosage forms until a sensation offullness is achieved. The polymer then degrades over time and/or isde-polymerized by ingestion of a specific substance, e.g., ade-polymerizer including, without any limitation, an agent that iscapable of raising the pH in the stomach or an intestinal enzyme orderivatives thereof.

Examples of intestinal enzymes include amylase, which hydrolyzes starchinto a mixture of maltose and glucose; lipase, which hydrolyzes ingestedfats into a mixture of fatty acids and monoglycerides (and its actionmaybe enhanced by the detergent effect of bile); trypsin, which cleavespeptide bonds on the C-terminal side of arginines and lysines;chymotrypsin, which cuts on the C-terminal side of tyrosine,phenylalanine, and tryptophan residues (the same bonds as pepsin, whoseaction ceases when the NaHCO.sub.3 raises the pH of the intestinalcontents); elastase, which cuts peptide bonds next to small, unchargedside chains such as those of alanine and serine; carboxypeptidase, whichremoves, one by one, the amino acids at the C-terminal of peptides;nucleases, which hydrolyze ingested nucleic acids (RNA and DNA) intotheir component nucleotides; aminopeptidases, which attack the aminoterminal (N-terminal) of peptides producing amino acids;disaccharidases, which convert disaccharides into their monosaccharidesubunits; maltase which hydrolyzes maltose into glucose, sucrase, whichhydrolyzes sucrose (common table sugar) into glucose and fructose; andlactase which hydrolyzes lactose (milk sugar) into glucose andgalactose.

The invention is desirable since the oral dosage forms are notmetabolically active and do not contain significant calories. Indeed,once the polymer has been de-polymerized and/or degraded, it simplypasses through the gastrointestinal tract and is excreted.

A further advantage provided by the invention is the temporary nature ofthe gastric volume reduction. With current treatments that result inreduction of gastric volume, including gastric bypass, gastricreduction, and intragastric balloons, a significant difficulty exists:adaptation of the stomach to its distended state. By allowing thestomach volume to be temporarily reduced and then returned to itsoriginal volume before being reduced again, the present inventionreduces the occurrence of stomach distension.

In addition to use in weight loss, the oral dosage forms and polymericformulations described herein are useful as safe, effective drugdelivery systems. The dosage forms and formulations described hereinallow for a longer residence time of a drug in the stomach without therisk of small bowel obstruction. Drugs that are taken orally on anhourly basis could instead be ingested on a daily basis using the oraldosage forms and polymeric formulations described herein. The inner coreof the oral dosage forms and polymeric formulations described hereinwould not contain any drug as this would cause a large bolus of drugrelease with passage and rapid dissolution into the intestine, but theouter layers can be infused with the drug as they must be dissolvedprior to any intestinal passage.

In one embodiment, the polymeric formulation provided by the presentinvention is useful for delivering drugs that, as a solid, areirritating to the gastrointestinal tract such as the mucosal surface orefficacious when administered in a sustained manner. For example,various antibiotics, especially antibiotics useful for eradicatingHelicobacter pylori from the submucosal tissue of the gastrointestinaltract can be delivered by the polymeric formulations of the presentinvention.

The invention provides methods for reducing gastric volume in a subjectin need thereof. The methods include administering to the subject aneffective amount of the oral dosage forms described herein. The dosageforms can be administered orally in the form of tablets, capsules,solutions, emulsions or suspensions. The compositions may be prepared inconventional forms, for example, capsules, tablets. Pharmaceuticalformulations containing compounds of this invention can be prepared byconventional techniques, e.g., as described in Remington'sPharmaceutical Sciences, 1985.

In one embodiment, the polymers of the present invention is formed intoa packed mass for ingestion, e.g., encapsulated as a “hard-filledcapsule” or a “soft-filled capsule” using any suitable encapsulatingprocedures and materials. The encapsulating material should be highlysoluble so that the polymer particles can be rapidly dispersed in thestomach after the capsule is ingested. In another embodiment, thepolymer of the present invention is formulated with a soluble binder andcompressed into a tablet or pill.

The pharmaceutical carrier or diluent employed may be a conventionalsolid or liquid carrier. Examples of solid carriers are lactose,sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate,stearic acid, or lower alkyl ethers of cellulose. Examples of liquidcarriers are syrup, peanut oil, olive oil, phospholipids, fatty acids,fatty acid amines, polyoxyethylene or water. The carrier or diluent mayinclude any sustained release material known in the art, such asglyceryl monostearate or distearate, alone or mixed with a wax.

If a solid carrier is used for oral administration, the preparation maybe tabletted or placed in a hard gelatin capsule in powder or pelletform. The amount of solid carrier will vary widely, but will usually befrom about 25 mg to about 1 gm. If a liquid carrier is used, thepreparation may be in the form of a syrup, emulsion, soft gelatincapsule, or sterile injectable liquid such as an aqueous or non-aqueousliquid suspension or solution.

Tablets are prepared by mixing the active ingredient withpharmaceutically inert, inorganic or organic carrier, diluents, and/orexcipients. Examples of such excipients which can be used for tabletsare lactose, maize starch or derivatives thereof, talc, stearic acid orsalts thereof. Examples of suitable excipients for gelatin capsules arevegetable oils, waxes, fats, semisolid, and liquid polyols.

The pharmaceutical products can additionally contain any of a variety ofadded components, such as, for example, preservatives, solubilizers,stabilizers, wetting agents, emulsifiers, sweeteners, colorants,flavorings, buffers, coating agents, antioxidants, diluents, and thelike.

Although the invention has been described with reference to the aboveexamples, it will be understood that modifications and variations areencompassed within the spirit and scope of the invention. Accordingly,the invention is limited only by the following claims.

1. A method of inducing weight lose in a patient comprising: providingingestible tablets comprising: a polymer that (i) swells upon absorbingwater from gastric fluid to increase its size, thereby promoting itsgastric retention, (ii) maintains its physical integrity in a stomachfor at least 2 hours, and (iii) is degradable by an intestinal enzyme orexposure to an intestinal pH, wherein the dosage form is in the form ofa tablet or capsule that maintains the polymer in a packed mass prior toits ingestion and then disintegrates in the gastric fluid to permit thepolymer to disperse in the stomach, wherein the polymer has a rate ofdegradation in an intestine environment higher than in a gastricenvironment, and wherein the rate of degradation is sufficiently rapidto substantially prevent a small bowel obstruction by the polymeringesting one or more ingestible tablets into the stomach of a patient,to achieve a sensation of fullness, thereby reducing gastric volume ofthe patient and inducing weight loss.
 2. The method of claim 1, wherein:the polymer is selected from the group consisting of polyvinyl alcohol,poly(ethyloxazoline), polyvinylacetate-polyvinylalcohol copolymers,poly(2-hydroxyethylacrylate-), poly(2-hydroxyethylmethacrylate),polyacrylic acid, and copolymers thereof, polysaccharides, water solubleproteins, and polynucleic acids. 3-18. (canceled)